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Primary cilia

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https://www.readbyqxmd.com/read/29345134/nanoscale-imaging-of-primary-cilia-with-scanning-ion-conductance-microscopy
#1
Yuanshu Zhou, Masaki Saito, Takafumi Miyamoto, Pavel Novak, Andrew I Shevchuk, Yuri E Korchev, Takeshi Fukuma, Yasufumi Takahashi
Primary cilia are hair-like sensory organelles whose dimensions and location vary with cell type and culture condition. Herein, we employed scanning ion conductance microscopy (SICM) to visualize the topography of primary cilia from different cell types. By combining SICM with fluorescence imaging, we successfully distinguished between surface cilia that project outward from the cell surface and subsurface cilia that are trapped below it. The nanoscale structure of the ciliary pocket, which cannot be easily identified using a confocal fluorescence microscope, was observed in SICM images...
January 18, 2018: Analytical Chemistry
https://www.readbyqxmd.com/read/29339787/cilia-related-protein-spef2-regulates-osteoblast-differentiation
#2
Mari S Lehti, Henna Henriksson, Petri Rummukainen, Fan Wang, Liina Uusitalo-Kylmälä, Riku Kiviranta, Terhi J Heino, Noora Kotaja, Anu Sironen
Sperm flagellar protein 2 (SPEF2) is essential for motile cilia, and lack of SPEF2 function causes male infertility and primary ciliary dyskinesia. Cilia are pointing out from the cell surface and are involved in signal transduction from extracellular matrix, fluid flow and motility. It has been shown that cilia and cilia-related genes play essential role in commitment and differentiation of chondrocytes and osteoblasts during bone formation. Here we show that SPEF2 is expressed in bone and cartilage. The analysis of a Spef2 knockout (KO) mouse model revealed hydrocephalus, growth retardation and death prior to five weeks of age...
January 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29337054/deficiency-of-primary-cilia-in-kidney-epithelial-cells-induces-epithelial-to-mesenchymal-transition
#3
Sang Jun Han, Jin Ki Jung, Seung-Soon Im, Seong-Ryong Lee, Byeong-Churl Jang, Kwon Moo Park, Jee In Kim
Primary cilium is a microtubule-based non-motile organelle that plays critical roles in kidney pathophysiology. Our previous studies revealed that the lengths of primary cilia decreased upon renal ischemia/reperfusion injury and oxidative stress, and restored with recovery. Here, we tested the hypothesis that lack of primary cilium causes epithelial to mesenchymal transition (EMT) of kidney tubule cells. We investigated the alteration of length of primary cilia in TGF-β-induced EMT via visualization of primary cilia by fluorescence staining against acetylated α-tubulin...
January 11, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29335527/myosin-va-is-required-for-preciliary-vesicle-transportation-to-the-mother-centriole-during-ciliogenesis
#4
Chien-Ting Wu, Hsin-Yi Chen, Tang K Tang
Primary cilia play essential roles in signal transduction and development. The docking of preciliary vesicles at the distal appendages of a mother centriole is an initial/critical step of ciliogenesis, but the mechanisms are unclear. Here, we demonstrate that myosin-Va mediates the transportation of preciliary vesicles to the mother centriole and reveal the underlying mechanism. We also show that the myosin-Va-mediated transportation of preciliary vesicles is the earliest event that defines the onset of ciliogenesis...
January 15, 2018: Nature Cell Biology
https://www.readbyqxmd.com/read/29332341/association-of-the-combined-parameters-including-the-frequency-of-primary-cilia-cd8-tumor-infiltrating-lymphocytes-and-pd-1-expression-with-the-outcome-in-intestinal-cancer
#5
Josef Dvorak, Dimitar Hadzi Nikolov, Ladislav Dusek, Alzbeta Filipova, Igor Richter, David Buka, Ales Ryska, Jaroslav Mokry, Stanislav Filip, Bohuslav Melichar, Tomas Buchler, Jitka Abrahamova
PURPOSE: Primary cilium (PC) is considered to be a functional homologue of the immune synapse. Microtubule structures, PC of cancer associated fibroblasts and immune synapses between cytotoxic CD8+ tumor infiltrating lymphocytes (TILs) and cancer cells, are regularly found in varying amounts in the microenvironment of solid tumors. The purpose of this study was to find out the potential association and combined prognostic significance of the frequency of PC, PD-1 and CD8+ TILs in patients with intestinal cancer...
November 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29330965/intra-hepatic-bile-duct-primary-cilia-in-biliary-atresia
#6
Roberta Frassetto, Filippo Parolini, Salvatore Marceddu, Giulia Satta, Valeria Papacciuoli, Maria Antonia Pinna, Alessandra Mela, Giannina Secchi, Grazia Galleri, Roberto Manetti, Luisa Bercich, Vincenzo Villanacci, Antonio Dessanti, Roberto Antonucci, Francesco Tanda, Daniele Alberti, Kathleen B Schwarz, Maria Grazia Clemente
AIM: The etiopathogenesis of non-syndromic biliary atresia (BA) is obscure. The primary aim was to investigate intra-hepatic bile duct cilia (IHBC) in BA at the diagnosis and correlation with clinical outcome. The secondary aim was to analyze IHBC in routine paraffin-embedded liver biopsies using conventional scanning electron microscopy (SEM). METHODS: Surgical liver biopsies taken at the diagnosis from 22 BA infants (age range: 39 - 116 days) and from 8 children with non-BA chronic cholestasis (age range: 162 days -16,8 years) were evaluated for IHBC, both by immunofluorescence (IF) and by SEM...
January 13, 2018: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/29327175/microrna-30c-as-a-novel-diagnostic-biomarker-for-primary-and-secondary-b-cell-lymphoma-of-the-cns
#7
Alexander Baraniskin, Monika Chomiak, Guido Ahle, Thomas Gress, Malte Buchholz, Michael Turewicz, Martin Eisenacher, Michelle Margold, Uwe Schlegel, Wolff Schmiegel, Stephan Hahn, Roland Schroers
Primary lymphomas of the central nervous system (PCNSL) are highly aggressive tumors affecting exclusively the CNS, meninges, and eyes. PCNSL must be separated from secondary spread of systemic lymphoma to the CNS (SCNSL), which may occur at diagnosis or relapse of systemic lymphomas. At present, there are no valid methods to distinguish PCNSL from SCNSL based on tumor biopsy because of similar histological presentation. However, SCNSL and PCNSL are different in terms of prognosis and adequate therapy protocols...
January 11, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29323929/variation-in-cilia-protein-genes-and-progression-of-lung-disease-in-cystic-fibrosis
#8
Elizabeth Blue, Tin L Louie, Jessica X Chong, Scott J Hebbring, Kathleen C Barnes, Nicholas M Rafaels, Michael R Knowles, Ronald L Gibson, Michael J Bamshad, Mary J Emond
RATIONALE: Cystic fibrosis, like primary ciliary dyskinesia, is an autosomal recessive disorder characterized by abnormal mucociliary clearance and obstructive lung disease. We hypothesized that genes underlying the development or function of cilia may modify lung disease severity in persons with cystic fibrosis. OBJECTIVES: To test this hypothesis, we compared variants in 93 candidate genes in both upper and lower tertiles of lung function in a large cohort of children and adults with cystic fibrosis to a population control data set...
January 11, 2018: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/29321670/clinical-and-experimental-evidence-suggest-a-link-between-kif7-and-c5orf42-related-ciliopathies-through-sonic-hedgehog-signaling
#9
Reza Asadollahi, Justin E Strauss, Martin Zenker, Oliver Beuing, Simon Edvardson, Orly Elpeleg, Tim M Strom, Pascal Joset, Dunja Niedrist, Christine Otte, Beatrice Oneda, Paranchai Boonsawat, Silvia Azzarello-Burri, Deborah Bartholdi, Michael Papik, Markus Zweier, Cordula Haas, Arif B Ekici, Alessandra Baumer, Eugen Boltshauser, Katharina Steindl, Michael Nothnagel, Albert Schinzel, Esther T Stoeckli, Anita Rauch
Acrocallosal syndrome (ACLS) is an autosomal recessive neurodevelopmental disorder caused by KIF7 defects and belongs to the heterogeneous group of ciliopathies related to Joubert syndrome (JBTS). While ACLS is characterized by macrocephaly, prominent forehead, depressed nasal bridge, and hypertelorism, facial dysmorphism has not been emphasized in JBTS cohorts with molecular diagnosis. To evaluate the specificity and etiology of ACLS craniofacial features, we performed whole exome or targeted Sanger sequencing in patients with the aforementioned overlapping craniofacial appearance but variable additional ciliopathy features followed by functional studies...
January 10, 2018: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/29321663/lpa-signaling-is-regulated-through-the-primary-cilium-a-novel-target-in-glioblastoma
#10
Yuriy V Loskutov, Caryn L Griffin, Kristina M Marinak, Andrey Bobko, Naira V Margaryan, Werner J Geldenhuys, Jann N Sarkaria, Elena N Pugacheva
The primary cilium is a ubiquitous organelle presented on most human cells. It is a crucial signaling hub for multiple pathways including growth factor and G-protein coupled receptors. Loss of primary cilia, observed in various cancers, has been shown to affect cell proliferation. Primary cilia formation is drastically decreased in glioblastoma (GBM), however, the role of cilia in normal astrocyte or glioblastoma proliferation has not been explored. Here, we report that loss of primary cilia in human astrocytes stimulates growth rate in a lysophosphatidic acid (LPA)-dependent manner...
January 11, 2018: Oncogene
https://www.readbyqxmd.com/read/29311635/subcellular-localization-of-mc4r-with-adcy3-at-neuronal-primary-cilia-underlies-a-common-pathway-for-genetic-predisposition-to-obesity
#11
Jacqueline E Siljee, Yi Wang, Adelaide A Bernard, Baran A Ersoy, Sumei Zhang, Aaron Marley, Mark Von Zastrow, Jeremy F Reiter, Christian Vaisse
Most monogenic cases of obesity in humans have been linked to mutations in genes encoding members of the leptin-melanocortin pathway. Specifically, mutations in MC4R, the melanocortin-4 receptor gene, account for 3-5% of all severe obesity cases in humans 1-3 . Recently, ADCY3 (adenylyl cyclase 3) gene mutations have been implicated in obesity 4,5 . ADCY3 localizes to the primary cilia of neurons 6 , organelles that function as hubs for select signaling pathways. Mutations that disrupt the functions of primary cilia cause ciliopathies, rare recessive pleiotropic diseases in which obesity is a cardinal manifestation 7 ...
January 8, 2018: Nature Genetics
https://www.readbyqxmd.com/read/29305615/primary-cilia-proteins-ciliary-and-extraciliary-sites-and-functions
#12
REVIEW
Kiet Hua, Russell J Ferland
Primary cilia are immotile organelles known for their roles in development and cell signaling. Defects in primary cilia result in a range of disorders named ciliopathies. Because this organelle can be found singularly on almost all cell types, its importance extends to most organ systems. As such, elucidating the importance of the primary cilium has attracted researchers from all biological disciplines. As the primary cilia field expands, caution is warranted in attributing biological defects solely to the function of this organelle, since many of these "ciliary" proteins are found at other sites in cells and likely have non-ciliary functions...
January 5, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29298421/primary-cilium-mediated-retinal-pigment-epithelium-maturation-is-disrupted-in-ciliopathy-patient-cells
#13
Helen Louise May-Simera, Qin Wan, Balendu Shekhar Jha, Juliet Hartford, Vladimir Khristov, Roba Dejene, Justin Chang, Sarita Patnaik, Quanlong Lu, Poulomi Banerjee, Jason Silver, Christine Insinna-Kettenhofen, Dishita Patel, Mostafa Lotfi, May Malicdan, Nathan Hotaling, Arvydas Maminishkis, Rupa Sridharan, Brian Brooks, Kiyoharu Miyagishima, Meral Gunay-Aygun, Rajarshi Pal, Christopher Westlake, Sheldon Miller, Ruchi Sharma, Kapil Bharti
Primary cilia are sensory organelles that protrude from the cell membrane. Defects in the primary cilium cause ciliopathy disorders, with retinal degeneration as a prominent phenotype. Here, we demonstrate that the retinal pigment epithelium (RPE), essential for photoreceptor development and function, requires a functional primary cilium for complete maturation and that RPE maturation defects in ciliopathies precede photoreceptor degeneration. Pharmacologically enhanced ciliogenesis in wild-type induced pluripotent stem cells (iPSC)-RPE leads to fully mature and functional cells...
January 2, 2018: Cell Reports
https://www.readbyqxmd.com/read/29290584/crispr-screens-uncover-genes-that-regulate-target-cell-sensitivity-to-the-morphogen-sonic-hedgehog
#14
Ganesh V Pusapati, Jennifer H Kong, Bhaven B Patel, Arunkumar Krishnan, Andreas Sagner, Maia Kinnebrew, James Briscoe, L Aravind, Rajat Rohatgi
To uncover regulatory mechanisms in Hedgehog (Hh) signaling, we conducted genome-wide screens to identify positive and negative pathway components and validated top hits using multiple signaling and differentiation assays in two different cell types. Most positive regulators identified in our screens, including Rab34, Pdcl, and Tubd1, were involved in ciliary functions, confirming the central role for primary cilia in Hh signaling. Negative regulators identified included Megf8, Mgrn1, and an unannotated gene encoding a tetraspanin protein we named Atthog...
December 26, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29287472/cover-image-volume-119-number-2-february-2018
#15
Ni Qiu, Wei-Jin Fang, Hong-Sheng Li, Zhi-Min He, Zhou-Sheng Xiao, Yan Xiong
Cover: The cover image, by Qiu et al., is based on the Original Research Article, Impairment of primary cilia contributes to visceral adiposity of high fat diet-fed mice, DOI: 10.1002/jcb.26253.
February 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29281629/loss-of-function-of-the-ciliopathy-protein-cc2d2a-disorganizes-the-vesicle-fusion-machinery-at-the-periciliary-membrane-and-indirectly-affects-rab8-trafficking-in-zebrafish-photoreceptors
#16
Irene Ojeda Naharros, Matthias Gesemann, José M Mateos, Gery Barmettler, Austin Forbes, Urs Ziegler, Stephan C F Neuhauss, Ruxandra Bachmann-Gagescu
Ciliopathies are human disorders caused by dysfunction of primary cilia, ubiquitous organelles involved in transduction of environmental signals such as light sensation in photoreceptors. Concentration of signal detection proteins such as opsins in the ciliary membrane is achieved by RabGTPase-regulated polarized vesicle trafficking and by a selective barrier at the ciliary base, the transition zone (TZ). Dysfunction of the TZ protein CC2D2A causes Joubert/Meckel syndromes in humans and loss of ciliary protein localization in animal models, including opsins in retinal photoreceptors...
December 27, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29278208/identification-of-the-multifaceted-chemopreventive-activity-of-curcumin-against-the-carcinogenic-potential-of-the-food-additive-kbro3
#17
Ismael Obaidi, Michael Higgins, Bojlul Bahar, Jessica L Davis, Tara McMorrow
BACKGROUND: Potassium bromate (KBrO3), a food additive, has been used in many bakery products as an oxidizing agent. It has been shown to induce renal cancer in many in-vitro and in-vivo experimental models Objectives: This study evaluated the carcinogenic potential of potassium bromate (KBrO3) and the chemopreventive mechanisms of the anti-oxidant and anti-inflammatory phytochemical, curcumin against KBrO3-induced carcinogenicity Method: Lactate dehydrogenase (LDH) cytotoxicity assay and morphological characteristics were used to assess curcumin's cytoprotective potential against KBrO3 toxicity...
December 26, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29276419/lessons-from-unilateral-loss-of-cilia-early-nasal-nitric-oxide-gas-mixing-and-the-role-of-sinus-patency-in-determining-nasal-nitric-oxide
#18
Kenneth Rodriguez, Benjamin Gaston, Jay Wasman, Nadzeya Marozkina
Nasal nitric oxide (nNO) measurement is a diagnostic test for primary ciliary dyskinesia (PCD). Here, we have shown the development of unilateral PCD-like symptoms associated with low nNO. A 60-year-old man had been previously healthy but developed unilateral, severe pansinusitis. He required surgical drainage of all left sinuses, and biopsies showed loss of the ciliated epithelium. At 4 weeks, he had unilateral (left-sided), profuse, clear rhinorrhea characteristic of PCD, and his surgical ostia were all patent endoscopically...
2017: Clinical Medicine Insights. Ear, Nose and Throat
https://www.readbyqxmd.com/read/29246855/technological-strategies-to-estimate-and-control-diffusive-passage-times-through-the-mucus-barrier-in-mucosal-drug-delivery
#19
Jay M Newby, Ian Seim, Martin Lysy, Yun Ling, Justin Huckaby, Samuel K Lai, M Gregory Forest
In mucosal drug delivery, two design goals are desirable: 1) insure drug passage through the mucosal barrier to the epithelium prior to drug removal from the respective organ via mucus clearance; and 2) design carrier particles to achieve a prescribed arrival time and drug uptake schedule at the epithelium. Both goals are achievable if one can control "one-sided" diffusive passage times of drug carrier particles: from deposition at the mucus interface, through the mucosal barrier, to the epithelium. The passage time distribution must be, with high confidence, shorter than the timescales of mucus clearance to maximize drug uptake...
December 12, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/29237719/ift20-modulates-ciliary-pdgfr%C3%AE-signaling-by-regulating-the-stability-of-cbl-e3-ubiquitin-ligases
#20
Fabian Marc Schmid, Kenneth Bødtker Schou, Martin Juel Vilhelm, Maria Schrøder Holm, Loretta Breslin, Pietro Farinelli, Lars Allan Larsen, Jens Skorstengaard Andersen, Lotte Bang Pedersen, Søren Tvorup Christensen
Primary cilia have pivotal roles as organizers of many different signaling pathways, including platelet-derived growth factor receptor α (PDGFRα) signaling, which, when aberrantly regulated, is associated with developmental disorders, tumorigenesis, and cancer. PDGFRα is up-regulated during ciliogenesis, and ciliary localization of the receptor is required for its appropriate ligand-mediated activation by PDGF-AA. However, the mechanisms regulating sorting of PDGFRα and feedback inhibition of PDGFRα signaling at the cilium are unknown...
December 13, 2017: Journal of Cell Biology
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